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© Research
Publication : Biochemical pharmacology

Differential inhibitory effects of three nitric oxide donors on ornithine decarboxylase activity in human colon carcinoma cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Biochemical pharmacology - 15 Apr 1998

Blachier F, Briand D, Selamnia M, Robert V, Guihot G, Mayeur C

Link to Pubmed [PMID] – 9719478

Biochem. Pharmacol. 1998 Apr;55(8):1235-9

Ornithine decarboxylase (ODC, EC 4.1.1.17) is the enzyme responsible for the synthesis of polyamines, which are absolutely necessary for cell proliferation. In the present work, we tested the effects of 3 nitric oxide (NO) donors, namely, sodium nitroprusside (SNP), (Z)-1-(N-methyl-N-[6-(N-methylammoniohexyl)amino] diazen-1-ium-1,2-diolate (MAHMA/NO) and 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium (DEA/NO), on ODC activity in human-colon carcinoma cells (HT-29). SNP was the most effective inhibitor of ODC activity with a concentration of 8 micromol/L inducing 50% inhibition of basal activity. The effect of SNP was reversed by haemoglobin (Hb), but not by GSH or L-cysteine (CYS). Very little of the SNP in solution was degraded into nitrite, but the presence of cellular homogenate increased the production of nitrite. MAHMA/NO and DEA/NO were much less effective than SNP as ODC inhibitors, since the concentrations of these agents which induce 50% inhibition of basal activity were 20- to 60-fold higher than that of SNP. The effects of MAHMA/NO and DEA/NO were not reversed by haemoglobin. In solution, these latter 2 agents were totally degraded into nitrites. In conclusion, SNP on the one hand and MAHMA/NO and DEA/NO on the other appeared to release different NOx species with different efficiency on ODC activity.